The Division of Cancer Treatment and Diagnosis, NCI (DCTD) has embarked on a strategic initiative in its National Clinical Trials Network (NCTN) to define and discover new treatments for patients with Acute Myelogenous Leukemia/Myelodysplastic Syndrome (AML/MDS). As described in a recent report from the Institute of Medicine ?treatment for these patients has not changed in a substantive way in the last 40 years? demonstrating that advances in this area are critically needed. The primary goal of this initiative is to optimize therapeutic strategies for adult, young adult, and adolescent patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes (AML/MDS). This includes: ? A master screening protocol that evaluates patients for assignment to clinical trials. ? A data support structure that allows longitudinal analysis of sensitivity and resistance biomarkers in leukemia for discovery of new molecular targets ? Deciphering clonal selection in minimal residual disease ? Understanding mechanisms of resistance and response to therapy The long-term goals of the study are to: ? Identify biomarkers with the potential to optimize therapy selection in AML/MDS. ? Define molecular signatures that predict different response categories in AML/MDS. ? Define phenotype/genotype characteristics of response/resistance in AML/MDS that will be valid for diverse or specific classes of drugs with different mechanisms of action. ? To identify targets in minimal residual disease (MRD), including targets in relapse and to identify new ways to eradicate MRD.